Purpose:
LHON is a maternally inherited disease characterized by sudden and profound loss of central vision in both eyes. The purpose of this study is to describe the 4 year results of treating LHON with a novel experimental quinone, EPI-743, in 7 consecutively enrolled patients all with the 11778 LHON mutation.

Methods:
Seven of 11 affected LHON patients treated with EPI-743 as part of this clinical study have been on continuous therapy for 4 years. Outcome measurements of efficacy include visual acuity (VA) (improvement if 2 or more lines of change or off to on chart), visual fields (VF) (improvement if >5dB of changes in mean deviation), OCT, and color vision (improvement if ≥ 2 plates in Ishihara plates, or from 0 to 2 plate). Thirteen eyes of 7 patients were included (one patient had retinal detachment in one eye) and two time points were compared, 6 months post onset and their most recent visit between 36-48 months into therapy. After six months, the natural history for affected patient with the 11778 LHON mutation is for vision to either stabilize or slowly deteriorate. This information is presented and discussed in a separate abstract submission.

Results:
VA: Nine of 13 eyes improved (70%), one to 20/20 level (from 20/300) and 8 from off chart to on chart. 4 eyes (30%) of 2 patients remained off chart. VF: 4 (30%) eyes improved, 8 (62%) were unchanged and 1 (8%) was worse than the 6 month VF. Color: 3 eyes (24%) improved (one 3/14 to 7/14, rest 0/14 to 2/14), 5 eyes (38%) were able to see only 1 color plate, and 5 eyes (38%) remained unable to see any color plates. OCT: All patients presented with progressive loss of fibers over time (25 to 50% of the normal values). These improvements were favorable in comparison to the natural history of 11778 LHON.

Conclusions:
EPI-743 treatment improved vision by these criteria in 56% of treated eyes. Visual improvement was noted up to 4 years following initiation of therapy suggesting that there is a large therapeutic window for recovery with EPI-743. There were no significant drug-related adverse events or clinical laboratory abnormalities. EPI-743 is a safe and effective treatment for LHON for most patients. This data is part of an ongoing compassionate use study.